Methods and compositions for diagnosis and treatment of cancer

Abstract

The present invention relates to the identification of nucleic acid and amino acid sequences that are characteristic of colorectal, in particular colonic, and gastric tumor tissues and colorectal, in particular colonic, and gastric tissues, and which represent targets for therapy or diagnosis of such tumor diseases in a subject.

Description

[0001]Gastrointestinal cancer (cancer of the digestive system) includes cancers of the esophagus, gallbladder, liver, pancreas, stomach, small intestine, large intestine (colon) and rectum. Some form of gastrointestinal cancer amounts to about 20 percent of all newly diagnosed cancers every year.[0002]Colorectal cancer includes cancerous growths in the colon, rectum and appendix. It is the third most common form of cancer and the second leading cause of cancer-related death in the Western world. Together, colon and rectal cancers account for 10% of cancers in men and 11% of cancers in women. It is the second most common site-specific cancer affecting both men and women. Many colorectal cancers are thought to arise from adenomatous polyps in the colon. These mushroom-like growths are usually benign, but some may develop into cancer over time. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Over 20% of patients present with metastatic (stage 1V...

AI Technical Summary

Benefits of technology

[0139]Immunisation with intact or substantially intact tumor antigen has the potential advantage of simultaneously immunising against both class I and class II epitopes but requires extensive and time-consuming efforts to purify large amounts of tumor antigen. The identification of MHC class I and class II peptides within a tumor antigen makes it possible to immunise with high levels of pure synthetic peptide. The peptide approach also has the advantage that one can choose between a MHC class I and a class II type response (or mixture) by choosing which epitopes to use. Immunisation with peptide also means that subdominant and / or cryptic epitopes can be chosen (as the need for antigen processing may be bypassed or reduced to a “trimming” role) in order to stimulate a different subset of T cells. Also the peptide may be modified (for example at their HLA class I or II anchor sites) to increase its immunogenicity.

[0235]Non-CDR regions of a mammalian antibody are known to be able to be replaced by similar regions of antibodies with the same or a different specificity, with the specificity for the epitope of the original antibody being retained. This made possible the development of “humanized” antibodies in which nonhuman CDRs are covalently linked to human FR and / or Fc / pFc′ regions to produce a functional antibody.

Problems solved by technology

These mushroom-like growths are usually benign, but some may develop into cancer over time.

Unfortunately, this protein may be made by other adenocarcinomas as well, or it may not be produced by a particular colon cancer.

Therefore, screening by chemical analysis for CEA has not been helpful.

However when it is detected at later stages (when distant metastases are present) it is less likely to be curable.

However, this circumstance is rare, occurring in less than 2% of all colon cancer cases.

Unfortunately, these patients eventually succumb to the disease, and this chemotherapy may not prolong survival or improve quality of life in Stage 1V patients.

Radiation has significant dose limits when residual bowel is exposed to it because the small and large intestine do not tolerate radiation well.

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